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NIH Grants $7.4 Million to UR Pediatrics Researchers

Elite Group Investigates Lung Damage due to Pneumocystis Carinii

October 09, 2002

The National Institutes of Health has chosen a team led by Francis Gigliotti, M.D., infectious disease specialist at Golisano Children’s Hospital at Strong, to investigate a deadly respiratory infection, pneumocystis carinii pneumonia (PcP).

This type of pneumonia is unique because it only strikes people with weakened immune systems, killing them if it is not diagnosed and treated quickly. The death rate can be as high as 40 percent, even with modern treatment.

As a pediatrician, Gigliotti first became interested in PcP in 1985, after he saw its effect on children with cancer. But today, it has become a widespread problem for anyone with a compromised immune system; in fact, adult AIDS patients are most at risk.

“Twenty years ago, pediatricians occupied themselves with trying to solve routine bacterial and viral infections in otherwise healthy children. They weren’t particularly interested in this bug,” says Gigliotti, Associate Chair of Academic Affairs in the Department of Pediatrics at the University of Rochester Medical Center. “It dawned on me that nobody really wanted to develop laboratory programs to study the infections that attacked children with weak immune systems. It was a large, under-served population, so I decided to pursue it.”

The $7.4 million award is the first ever “Program Project Grant” received by the Department of Pediatrics. PPGs are more prestigious grants, and therefore more difficult to obtain. They allow researchers to string together a series of scientific projects that might otherwise stand alone, and to add extra funding requests for new equipment, travel, and administration of the overall program.

The grant is an excellent example of the Medical Center’s progress toward a strategic goal of expanding collaborative research. The pediatrics team cited in its NIH application the university’s newly built, 9,000 square feet of laboratory space for lung biology research, and a decades-long history of strong collaboration between infectious disease and neonatal pulmonary specialists here.

The objective of the five-year study is to find a way to control the body’s inflammatory response to the pneumocystis carinii fungus. Although antibiotics are often effective at wiping it out, it can take a week before the drugs take hold. So, the goal of treatment is to buy time before a patient declines and must be put on a ventilator, when the prognosis becomes grim. The death rate for patients on a ventilator with advanced PcP can be as high as 90 percent, Gigliotti says.

When PcP invades the lungs, the body’s natural response is to unleash infection-fighting white cells. But sometimes this vigorous inflammatory response ends up damaging the lungs more than the infection itself, preliminary data have shown. In fact, acting on observations made by Terry W. Wright, Ph.D., then a post-doctoral trainee in Pediatrics at the UR, Gigliotti and Wright developed models of p. carinii that were able to show that controlling the body’s immune response during the infection holds the key to successful treatment.

The Medical Center team will conduct three separate investigations to check the hypothesis that controlling the immune response might prevent lung damage. In the final stage, the researchers will evaluate potential new approaches to therapy for PcP. Besides Gigliotti and Wright, faculty members from the Department of Pediatrics having key roles in the project are: Jacob N. Finkelstein, Ph.D.; Robert H. Notter, M.D. Ph.D.; Michael A. O’Reilly, Ph.D.; Gloria Pryhuber, M.D.; Patricia R. Chess, M.D.; and Allen Harmsen, Ph.D., chair of Veterinary Molecular Biology at Montana State University. # # #